Onconova Therapeutics, Inc. announced new preclinical data characterizing rigosertib’s mechanisms of action in a poster at the American Association for Cancer Research Special Conference on Targeting RAS (AACR Targeting RAS Conference). Preclinical studies featured in the poster evaluated mechanisms by which rigosertib may activate an anti-cancer immune response and inhibit the RAS-MAPK pathway. Results indicate that rigosertib stimulates an immune response via activation of the NLRP3 inflammasome, which leads to the secretion of the pro-inflammatory cytokines IL-1ß and IL-18.

Additional data identified the proteins NQO2, ERO1A, and NEK7 as potential novel targets that may be modulated by rigosertib. Activation of NQO2 and/or ERO1A leads to reactive oxygen species (ROS)-induced activation of JNK signaling, which in-turn leads to RAS-MAPK pathway inhibition. Rigosertib interaction with NEK7 could possibly cause the destabilization of microtubules and cell cycle arrest in mitosis, which are critical for cell division.